The long-term objective of this proposal is to determine if in vitro-derived retinal progenitor cells can be used as a form of treatment for retinal diseases. The irreversible loss of photoreceptors is the cause of blindness in many inherited retinal diseases. To address this problem, retinal progenitor cells may have the potential to generate these once thought irreplaceable cells. We have developed an in vitro method of deriving a form of retinal progenitors;we call induced-multipotent retinal cells (iRC). iRCs are sufficient to generate mature retinal cell classes in vitro, and also functional eyes in vivo. The goals of my study are to determine if iRCs can generate mature retinal cell classes in a normal and degenerated mature retina. The specific aims are Aim 1: Determine the fate of iRCs transplanted into the mature retina. I will first determine if transplanted iRCs can survive, differentiate into retinal cell classes, and structurally integrate into a mature retina. Aim 2: Determine the fate of iRCs in a degenerated retina. I will first determine the conditions to maintain a rod- deficient retina in transgenic Xenopus. Next, I will transplant iRCs into the rod-deficient retina and determine if they survive, differentiate, and structurally integrate. The fate of iRCs will be determined using a criterion for cell morphology, immunohistochemistry, and location within the retina. The rationale for these experiments is that identification of the cell classes derived from iRCs will set the foundation for influencing iRCs to differentiate primarily toward the rod photoreceptor fate and testing for any functional improvement in scotopic (rod specific) vision. Determining if iRCs can generate mature retinal cell classes in a normal and degenerated mature retina will pave the way for understanding how to develop therapies for retinal diseases that cause blindness.